Variant chrX-133026081-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031907.3(USP26):c.2140A>G(p.Ile714Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,096,777 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.0000055 ( 0 hom. 1 hem. )

Consequence

USP26
NM_031907.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.701

Variant links:

Genes affected

USP26 (HGNC:13485): (ubiquitin specific peptidase 26) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases and is a deubiquitinating enzyme (DUB) with His and Cys domains. It is specifically expressed in testis tissue. Mutations in this gene have been associated with Sertoli cell-only syndrome and male infertility. [provided by RefSeq, Jul 2008]

USP26 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048077732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP26	NM_031907.3 linkuse as main transcript	c.2140A>G	p.Ile714Val	missense_variant	6/6	ENST00000511190.6	NP_114113.1	Q9BXU7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP26	ENST00000511190.6 linkuse as main transcript	c.2140A>G	p.Ile714Val	missense_variant	6/6	2	NM_031907.3	ENSP00000423390.1		Q9BXU7
USP26	ENST00000370832.1 linkuse as main transcript	c.2140A>G	p.Ile714Val	missense_variant	1/1	6		ENSP00000359869.1		Q9BXU7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

182349

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67525

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1096777

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362217

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000357

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.2140A>G (p.I714V) alteration is located in exon 1 (coding exon 1) of the USP26 gene. This alteration results from a A to G substitution at nucleotide position 2140, causing the isoleucine (I) at amino acid position 714 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0020

DANN

Benign

0.28

DEOGEN2

Benign

0.00047

T;T

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.25

.;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.32

N;N

REVEL

Benign

0.020

Sift

Benign

0.43

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0

B;B

Vest4

0.043

MutPred

0.42

Loss of methylation at K718 (P = 0.0827);Loss of methylation at K718 (P = 0.0827);

MVP

0.35

MPC

0.051

ClinPred

0.017

GERP RS

-7.3

Varity_R

0.025

gMVP

0.039

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over